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Cell Contact and Pressure Control of YAP Localization and Clustering Revealed by Super-resolution Imaging

Abstract

Yes-associated protein (YAP) is well known for being an effecter of the Hippo signaling cascade that plays a critical role in organ size control, tumorigenesis and regeneration. As YAP is a transcriptional coactivator, nuclear accumulation is a crucial determinant of its function. Numerous investigations have provided insights into the regulation of YAP, such as upstream molecules of the Hippo pathway, cell contact inhibition and mechanical forces. However, the detailed information of YAP spatial localization and organization in cells remains uncertain, and how mechanical signals control YAP distribution and function is not fully known. Therefore, we used one of super-resolution imaging techniques, dSTORM, combined with confocal microscopy, to solve these problems. We find that YAP is mainly distributed in clusters in cells, and that both cell contact and pressure on cell surfaces promote the nuclear-to-cytoplasm translocation of YAP and its phosphorylation, whereas weaken the clustering of nuclear YAP and its transcriptional activity. Moreover, we find that pressure regulation may be more effective to YAP from cancer cells than normal cells, which could help open a door to target YAP for anticancer drug design.

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Publication details

The article was received on 07 Aug 2017, accepted on 12 Oct 2017 and first published on 13 Oct 2017


Article type: Paper
DOI: 10.1039/C7NR05818G
Citation: Nanoscale, 2017, Accepted Manuscript
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    Cell Contact and Pressure Control of YAP Localization and Clustering Revealed by Super-resolution Imaging

    H. Wang, J. gao, L. He, Y. Shi, M. Cai, H. Xu, J. Jiang and L. Zhang, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR05818G

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